The objective of this research proposal is to define the action of gastro-intestinal hormones and tissue substances on colonic tumor growth, vascularity, and metabolism of drugs. This objective will enable us to identify the influence of intestinal substances on the efficacy of chemotherapy and to examine the role of intestinal substances in such concepts as local regulation of neoplastic growth and the genesis of neoplasia on the basis of excessive or deficient production of intestinal substances. In the initial phases of this project we will determine the effects of the gastrointestinal hormones, gastrin, secretin, and cholecystokinin and prostaglandin E2 which have been shown to exert trophic effects on the mucosa of the gastrointestinal tract, on the growth of colonic tumors. We will use transplantable colonic carcinoma lines developed in rats as well as cells maintained in tissue culture. We will determine growth by measuring the size of the tumor or by cell number per plate after hormone treatment or by the rate of DNA, RNA, and protein synthesis using radioactive precursors. Since most of the gastrointestinal hormones and tissue substances are vasoactive agents, we will also determine the effects of these agents on the vascularity of the tumor by radioactive microsphere estimation of tissue blood flow, Rb86 clearance, and histological and electronmicroscopic examination of vascular patterns in colonic tumors. We will also determine the effects of these agents on the metabolism of drugs by colonic tumors. As these approaches develop, we will study other gastrointestinal hormones and tissue substances.